This Article Full Text Full Text (PDF) Online Supplement All Versions of this Article: 200609-1274OCv1 175/3/263    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Huqun Articles by Hagiwara, K. Search for Related Content PubMed PubMed Citation Articles by Huqun, Articles by Hagiwara, K.

Mutations in the SLC34A2 Gene Are Associated with Pulmonary Alveolar Microlithiasis

Departments of Respiratory Medicine, Pathology, and Chest Surgery, Saitama Medical University, Saitama; Department of Respiratory Oncology and Molecular Medicine, Tohoku University, Sendai; Department of Pulmonary Medicine, Disease Control and Prevention Center, International Medical Center of Japan; Department of Respiratory Medicine, Tama Hokubu Hospital; Department of Respiratory Medicine, Respiratory Center, Toranomon Hospital, Tokyo; Department of Cardiovascular Pharmacology, Yamagata University, Yamagata; Department of Respiratory Medicine, Katta General Hospital, Miyagi; Department of Respiratory Medicine, Kurashiki Central Hospital, Okayama; Third Department of Internal Medicine, Sapporo Medical University, Sapporo; Department of Surgery II, Fukushima Medical University, Fukushima; Clinical Research Center, National Hospital Organization, Kinki-chuo Chest Medical Center; and Osaka Kampo Medical Center, Osaka, Japan

Correspondence and requests for reprints should be addressed to Koichi Hagiwara, M.D., Ph.D., Professor, Department of Respiratory Medicine, Saitama Medical University, 38 Morohongo, Moroyama-machi, Iruma-gun, Saitama 350–0495, Japan. E-mail: hagiwark{at}saitama-med.ac.jp

Rationale: Pulmonary alveolar microlithiasis is an autosomal recessive disorder in which microliths are formed in the alveolar space.

Objectives: To identify the responsible gene that causes pulmonary alveolar microlithiasis.

Methods: By means of a genomewide single-nucleotide polymorphism analysis using DNA from three patients, we have narrowed the region in which the candidate gene is located. From this region, we have identified a gene that has mutations in all patients with pulmonary alveolar microlithiasis.

Measurements and Main Results: We identified a candidate gene, SLC34A2, that encodes a type IIb sodium phosphate cotransporter and that is mutated in six of six patients investigated. SLC34A2 is specifically expressed in type II alveolar cells, and the mutations abolished the normal gene function.

Conclusion: Mutations in the SLC34A2 gene that abolish normal gene function cause pulmonary alveolar microlithiasis.

Key Words: pulmonary alveolar microlithiasis • homozygosity mapping • GeneChip • single-nucleotide polymorphisms

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Pulmonary alveolar microlithiasis is an autosomal recessive disorder in which microliths are formed in the alveolar space. However, the responsible gene has not been identified. What This Study Adds to the Field Mutation of the SLC34A2 gene that encodes the sodium-dependent phosphate transporter causes pulmonary alveolar microlithiasis.

 

This article has been cited by other articles:

				Y. Sabbagh, S. P. O'Brien, W. Song, J. H. Boulanger, A. Stockmann, C. Arbeeny, and S. C. Schiavi Intestinal Npt2b Plays a Major Role in Phosphate Absorption and Homeostasis J. Am. Soc. Nephrol., November 1, 2009; 20(11): 2348 - 2358. [Abstract] [Full Text] [PDF]

				S. Chandra, A. Mohan, R. Guleria, P. Das, and C. Sarkar Bilateral stony lung: pulmonary alveolar microlithiasis BMJ Case Reports, May 8, 2009; 2009(may08_1): bcr0920081012 - bcr0920081012. [Abstract] [Full Text]

				Y Ishihara, K Hagiwara, K Zen, Huqun, Y Hosokawa, and A Natsuhara A case of pulmonary alveolar microlithiasis with an intragenetic deletion in SLC34A2 detected by a genome-wide SNP study Thorax, April 1, 2009; 64(4): 365 - 367. [Abstract] [Full Text] [PDF]

				S. Chandra, A. Mohan, R. Guleria, P. Das, and C. Sarkar Pulmonary alveolar microlithiasis BMJ Case Reports, March 17, 2009; 2009(mar08_1): bcr0920080919 - bcr0920080919. [Full Text]

				J. A Whitsett Hereditary disorders of surfactant homeostasis cause acute and chronic lung disease in infancy Thorax, April 1, 2008; 63(4): 295 - 296. [Full Text] [PDF]

				A. U. Wells and C. M. Hogaboam Update in Diffuse Parenchymal Lung Disease 2007 Am. J. Respir. Crit. Care Med., March 15, 2008; 177(6): 580 - 584. [Full Text] [PDF]